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Jin Z, Yan B, Zhang L, Wang C. Biological therapy in chronic rhinosinusitis with nasal polyps. Expert Rev Clin Immunol 2025; 21:473-492. [PMID: 39862235 DOI: 10.1080/1744666x.2025.2459929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 12/17/2024] [Accepted: 01/20/2025] [Indexed: 01/27/2025]
Abstract
INTRODUCTION Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease. High proportions of patients with CRSwNP characterized by type 2 inflammation fail to gain adequate control with conventional treatment. The application of biologics in clinics and assessments of novel biologics in clinical trials are blooming in expectations to fulfill the unmet medical needs of patients with CRSwNP with type 2 inflammation. AREAS COVERED After an extensive search of PubMed, Medline, and EMBASE for the most recent evidence, we thoroughly summarize current advances in biological therapies for treating patients with CRSwNP. EXPERT OPINION In recent years, biological therapy has been in the spotlight in clinical studies on CRSwNP. Biologics have proven to be efficacious in reducing nasal polyp size, alleviating CRSwNP-related symptoms, improving quality of life, and reducing the need for systemic corticosteroids or endoscopic sinus surgery for nasal polyps. The considerable efficacy and safety profile of biologics has offered patients with refractory CRSwNP another treatment option. However, some concerns remain to be addressed. Aspects such as the position of biological therapy in the management of CRSwNP, traits of patients suitable for certain biologics, etc. necessitate efforts to elucidate these unknowns in order to provide patients with tailored therapy.
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Affiliation(s)
- Zeyi Jin
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Bing Yan
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Luo Zhang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Chengshuo Wang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
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Lee JY, Kim DH, Kim SW, Im YH, Park CS, Kim DH, Alkhars Z, Kim SW. Diagnostic criteria for eosinophilic chronic rhinosinusitis: Comparative analysis and novel scoring system. Int Forum Allergy Rhinol 2024; 14:1746-1756. [PMID: 39039646 DOI: 10.1002/alr.23416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 06/25/2024] [Accepted: 07/05/2024] [Indexed: 07/24/2024]
Abstract
BACKGROUND Accurate identification of eosinophilic chronic rhinosinusitis is essentialg because its treatment and prognosis substantially differ from other subtypes. METHODS This retrospective observational study included 640 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis in a single tertiary center from January 2021 to December 2022. Receiver operating characteristic curves were generated to compare accuracy, sensitivity, specificity of the novel scoring system, and previous diagnostic criteria (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, European Forum for Research and Education in Allergy and Airway Diseases, European Position Paper on Rhinosinusitis and Nasal Polyps, and Sakuma et al.) for predicting eosinophilic chronic rhinosinusitis (ECRS) by tissue eosinophil count ≥70 per high power field. RESULTS Patients were randomly divided into estimation (n = 430) and validation (n = 210) groups. The area under the receiver operating characteristic curve for the novel score was 0.753 (95% confidence interval [CI], 0.670-0.835) in the estimation group, 0.729 (0.629-0.830) in the validation group, and 0.661 (0.584-0.738) in the 20-fold cross-validation with the entire dataset. CONCLUSIONS We propose a novel scoring system that incorporates three key parameters: "novel score = blood eosinophil (%) + total Lund-Mackay score of anterior ethmoid sinuses + 2 if nasal polyp present" greater than 7 can be reliably used for diagnosing ECRS. This system can facilitate decision-making processes regarding the administration of oral steroids and biologics targeting type 2 inflammation prior to surgical intervention.
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Affiliation(s)
- Jae Yoon Lee
- Department of Otolaryngology-Head and Neck Surgery, Seoul Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Do Hyun Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Sung Won Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Yeon Hee Im
- Department of Otolaryngology-Head and Neck Surgery, Uijeongbu Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, South Korea
| | - Chan Soon Park
- Department of Otolaryngology-Head and Neck Surgery, Saint Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea
| | - Dong Hyun Kim
- Department of Otolaryngology-Head and Neck Surgery, Incheon Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
| | - Zainab Alkhars
- Department of Otolaryngology-Head and Neck Surgery, Al Jabr Hospital, Ministry of Health, Al Ahsa, Saudi Arabia
| | - Soo Whan Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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Cha H, Kim D, Lee HW, Lee Y, Baek BJ, Lee JY, Choi JH. Relationship between chronic rhinosinusitis and risk of obstructive sleep apnea. Sci Rep 2024; 14:21379. [PMID: 39271710 PMCID: PMC11399112 DOI: 10.1038/s41598-024-71923-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 09/02/2024] [Indexed: 09/15/2024] Open
Abstract
The relationship between obstructive sleep apnea (OSA) and chronic rhinosinusitis (CRS) has not yet been fully elucidated. Therefore, the objective of this study was to evaluate the connection between OSA risk and CRS by investigating associations between the STOP-Bang questionnaire and presence of CRS in a nationwide, population-based study. This is a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNHANES). We evaluated 10,081 subjects who completed both the STOP-Bang and CRS-related questionnaires. Among the total subjects, 390 (3.9%) were CRS patients. The median STOP-Bang score was 3.0 [2.0; 4.0] in CRS patients, compared to 2.0 [1.0; 3.0] in subjects without CRS. In a low-risk group according to the STOP-Bang questionnaire, 3.1% of subjects were CRS patients. However, a gradual increase was observed among different risk groups. In the higher risk group, CRS patients accounted for 5.3% (P < 0.001). Among the four main symptoms of CRS (nasal obstruction, nasal discharge, facial pain/pressure, and decreased sense of smell), nasal obstruction (4.1 to 7.3%) and a decreased sense of smell (1.9 to 3.3%) increased with higher STOP-Bang scores. This study found that the proportion of patients with CRS was significantly higher in the group at a higher STOP-Bang score in the general population. Among symptoms of CRS, nasal obstruction and anosmia were found to be associated with an increased STOP-Bang score.
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Affiliation(s)
- Hyunkyung Cha
- Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
| | - DoHyeon Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
| | - Hyeon Woo Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
| | - Yeongrok Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
| | - Byoung-Joon Baek
- Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
| | - Jae Yong Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon Hospital, 170 Jomaru-ro, Bucheon, 14584, Republic of Korea
| | - Ji Ho Choi
- Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon Hospital, 170 Jomaru-ro, Bucheon, 14584, Republic of Korea.
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Lin YT, Tsai MH, Su YY, Huang SC. Comparison of cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant patients in chronic rhinosinusitis with nasal polyps. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2024; 20:34. [PMID: 38773574 PMCID: PMC11110371 DOI: 10.1186/s13223-024-00896-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 04/29/2024] [Indexed: 05/24/2024]
Abstract
PURPOSE Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by inflammation of the nasal and sinus mucosa. The inflammatory patterns may differ among patients, leading to different subtypes based on the dominant inflammatory cell type. This study aimed to compare the differences in cytokine expression and disease severity between plasma cell-dominant and eosinophil-dominant subtypes in patients with CRSwNP. METHODS This study included 53 CRSwNP patients and 19 control subjects who did not have asthma or a history of cigarette smoking. The expression of cytokines and inflammatory cells was assessed via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. RESULTS Among the cytokines analyzed, only IL-6 was significantly different between the two subtypes. A greater proportion of mast cells and IgE cells was present in plasma cell-dominant CRSwNP patients than in eosinophil-dominant group. For the three disease severity scores (LMK-CT, TPS and SNOT-22), objective scores (LMK-CT and TPS) were greater in the eosinophil-dominant CRSwNP group, while the opposite result was shown for the subjective score (SNOT-22). Additionally, the percentage of plasma cell-dominant cells was significantly positively correlated with disease severity according to the TPS and SNOT-22 scores. CONCLUSIONS Our data revealed that plasma cell-dominant inflammation, a subtype of type 2 CRS, was significantly correlated with subjective disease severity. The study also highlights the role of IL-6, IgE and mast cells as distinguishing factors between eosinophil-dominant and plasma cell-dominant CRSwNP. This information could be useful for clinical diagnosis and personalized treatment.
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Affiliation(s)
- Yu-Tsai Lin
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
- Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.
- Department of Otolaryngology, Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Song District, Kaohsiung, 833, Taiwan.
| | - Ming-Hsien Tsai
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Yan-Ye Su
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Shun-Chen Huang
- Department of Anatomic Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan.
- Department of Anatomic Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, 123 Ta-Pei Road, Niao-Song District, Kaohsiung, 833, Taiwan.
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Jang JH, Yang EM, Lee Y, Shin YS, Ye YM, Park HS. Diagnostic biomarkers for chronic rhinosinusitis in adult asthmatics in real-world practice. World Allergy Organ J 2024; 17:100879. [PMID: 38380106 PMCID: PMC10877182 DOI: 10.1016/j.waojou.2024.100879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 01/06/2024] [Accepted: 01/27/2024] [Indexed: 02/22/2024] Open
Abstract
Background Chronic rhinosinusitis (CRS) is a common comorbid condition of asthma that affects the long-term outcome of asthmatic patients. CRS is a heterogeneous disease requiring multiple biomarkers to explain its pathogenesis. This study aimed to develop potential biomarkers for predicting CRS in adult asthmatic patients in a real-world clinical setting. Methods This study enrolled 108 adult asthmatic patients who had maintained anti-asthmatic medications, including medium-to-high doses of inhaled corticosteroid plus long-acting β2-agonists, and compared clinical characteristics between patients with CRS (CRS group) and those without CRS (non-CRS group). CRS was diagnosed based on the results of paranasal sinus X-ray and/or osteomeatal-unit CT as well as clinical symptoms. Type-2 parameters, including blood eosinophil count, serum levels of periostin/dipeptidyl peptidase 10 (DPP10) and clinical parameters, such as FEV1% and fractional exhaled nitric oxide (FeNO), were analyzed. All biomarkers were evaluated by logistic regression and classification/regression tree (CRT) analyses. Results The CRS group had higher blood eosinophil counts/FeNO levels and prevalence of aspirin-exacerbated respiratory disease (AERD) than the non-CRS group (n = 57, 52.8% vs. n = 75, 47.2%; P < 0.05), but no differences in sex/smoking status or asthma control status were noted. The CRS group had higher serum periostin/DPP10 levels than the non-CRS group. Moreover, logistic regression demonstrated that serum periostin/DPP10 and the AERD phenotype were significant factors for predicting CRS in asthmatic patients (adjusted odds ratio, 2.14/1.94/12.39). A diagnostic algorithm and the optimal cutoff values determined by CRT analysis were able to predict CRS with 86.27% sensitivity (a 0.17 negative likelihood ratio). Conclusion Serum periostin, DPP10 and the phenotype of AERD are valuable biomarkers for predicting CRS in adult asthmatic patients in clinical practice.
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Affiliation(s)
- Jae-Hyuk Jang
- Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Eun-Mi Yang
- Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Youngsoo Lee
- Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Yoo Seob Shin
- Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Young-Min Ye
- Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Hae-Sim Park
- Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
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Sima Y, Wang X, Zhang L. Interaction of eosinophilic and neutrophilic inflammation in patients with chronic rhinosinusitis. Curr Opin Allergy Clin Immunol 2024; 24:25-31. [PMID: 37966141 DOI: 10.1097/aci.0000000000000956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2023]
Abstract
PURPOSE OF REVIEW In the past year, the endotype of chronic rhinosinusitis (CRS) has been studied from a new perspective. Eosinophilic and neutrophilic inflammation are not independent processes in the pathogenesis of CRS. In this review, we will focus on recent research on mixed eosinophilic-neutrophilic inflammation in CRS and discuss the mechanism and potential treatments. RECENT FINDINGS Traditionally, patients with eosinophilic CRS (ECRS) present with severe clinical manifestations, comorbidities, and a higher recurrence rate. Recent studies have found that approximately 40% of patients with ECRS present with neutrophilic infiltration, while patients with predominantly eosinophilic infiltration along with neutrophilic inflammation present with more complex inflammation, clinical manifestations and exhibit refractory characteristics. SUMMARY The complex inflammatory profile and refractory clinical characteristics of mixed eosinophilic-neutrophilic inflammation in CRS are current challenges for clinicians. We summarize the features of eosinophilic and neutrophilic inflammation and current studies on the mechanisms of mixed eosinophilic-neutrophilic inflammation and suggest potentially effective therapeutic methods. We hope that this review will help with determining precise treatment options for patients.
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Affiliation(s)
- Yutong Sima
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University
- Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology
| | - Xiangdong Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University
- Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University
- Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
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Bai J, Tan BK, Kato A. Endotypic heterogeneity and pathogenesis in chronic rhinosinusitis. Curr Opin Allergy Clin Immunol 2024; 24:1-8. [PMID: 37966157 PMCID: PMC10873077 DOI: 10.1097/aci.0000000000000954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2023]
Abstract
PURPOSE OF REVIEW This review aims to provide updates in realms of endotypic heterogeneity, pathogenesis at the molecular level, potential of biomarkers, and cutting-edge scope of biologics in CRS. RECENT FINDINGS High-dimensional analyses, such as transcriptomes, and machine learning, have significantly enhanced CRS endotyping, uncovering diverse pathogenetic mechanisms contributing to its heterogeneity. The dynamic process of epithelial remodeling in CRS pathogenesis has gained more clarity and support as exemplified by IL-13 and oncostatin M (OSM) that are shown intricately linked to epithelial barrier dysfunction. Moreover, anti-dsDNA autoantibody, BAFF, periostin, and cystatin SN show promise as potentials biomarkers, offering diagnostic and prognostic value for CRS. SUMMARY The identification of inflammatory molecules involved in endotype specific signaling pathways provides insights into the underlying mechanisms and verifiable biomarkers for diagnosis and prediction of disease severity. More comprehensive clinical studies should be conducted to facilitate biologics from bench to bedside in treating CRS.
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Affiliation(s)
- Junqin Bai
- Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Bruce K. Tan
- Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Atsushi Kato
- Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
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Yoo SH, Kim YA, Mo JH. Can EPOS2020 criteria of type 2 inflammation be applied to Asian patients with chronic rhinosinusitis? Acta Otolaryngol 2023; 143:789-795. [PMID: 37837274 DOI: 10.1080/00016489.2023.2264898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 09/20/2023] [Indexed: 10/15/2023]
Abstract
BACKGROUND There is a large diversity of mucosal immunologic chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes across Western and Asian patient populations. OBJECTIVES The objective of the study was whether the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 criteria for type 2 inflammation are appropriate for biological use in CRSwNP patients. METHODS A total of 207 participants are enrolled for the study. Retrospective evaluations of the tissues taken during surgery and the patients' clinical features were performed. We investigated whether the criteria described in the EPOS2020 guideline were appropriate based on the criteria for type 2 inflammation identified based on prior studies using receiver-operating characteristic (ROC) analyses. RESULTS The EPOS 2020 criteria are also shown to be an insufficient evaluation approach with low specificity (area under curve [AUC] = 0.645, specificity 8.4%). The authors created a novel scoring method using the total serum IgE level, blood eosinophil percentage, and tissue eosinophil percentage. This novel scoring system (AUC = 0.862, p < .001) fared better in ROC analyses than the EPOS 2020 criteria (AUC = 0.645) and Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis scoring system (AUC = 0.647). CONCLUSIONS AND SIGNIFICANCE A novel standard for type 2 inflammation in Asian CRSwNP patients must be established, as the EPOS 2020 criteria do not appear to be sufficient.
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Affiliation(s)
- Shin Hyuk Yoo
- Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Korea
| | - Yoon-Ah Kim
- Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Korea
| | - Ji-Hun Mo
- Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Korea
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Zhou A, Shi C, Fan Y, Zheng Y, Wang J, Liu Z, Xie H, Liu J, Jiao Q. Involvement of CD40-CD40L and ICOS-ICOSL in the development of chronic rhinosinusitis by targeting eosinophils. Front Immunol 2023; 14:1171308. [PMID: 37325657 PMCID: PMC10267736 DOI: 10.3389/fimmu.2023.1171308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 03/20/2023] [Indexed: 06/17/2023] Open
Abstract
Background Chronic rhinosinusitis (CRS), whose prevalence and pathogenesis are age-related, is characterized by nasal tissue eosinophil infiltration. CD40-CD40 ligand (CD40L) pathway involves in the eosinophil-mediated inflammation, and inducible co-stimulator (ICOS)-ICOS ligand (ICOSL) signal can strengthen CD40-CD40L interaction. Whether CD40-CD40L and ICOS-ICOSL have a role in the development of CRS remains unknown. Objectives The aim of this study is to investigate the association of CD40-CD40L and ICOS-ICOSL expression with CRS and underlying mechanisms. Methods Immunohistology detected the expression of CD40, CD40L, ICOS, and ICOSL. Immunofluorescence was performed to evaluate the co-localizations of CD40 or ICOSL with eosinophils. Correlations between CD40-CD40L and ICOS-ICOSL as well as clinical parameters were analyzed. Flow cytometry was used to explore the activation of eosinophils by CD69 expression and the CD40 and ICOSL expression on eosinophils. Results Compared with the non-eCRS subset, ECRS (eosinophilic CRS) subset showed significantly increased CD40, ICOS, and ICOSL expression. The CD40, CD40L, ICOS, and ICOSL expressions were all positively correlated with eosinophil infiltration in nasal tissues. CD40 and ICOSL were mainly expressed on eosinophils. ICOS expression was significantly correlated with the expression of CD40-CD40L, whereas ICOSL expression was correlated with CD40 expression. ICOS-ICOSL expression positively correlated with blood eosinophils count and disease severity. rhCD40L and rhICOS significantly enhanced the activation of eosinophils from patients with ECRS. Tumor necrosis factor-α (TNF-α) and interleukin-5 (IL-5) obviously upregulated CD40 expression on eosinophils, which was significantly inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor. Conclusions Increased CD40-CD40L and ICOS-ICOSL expressions in nasal tissues are linked to eosinophils infiltration and disease severity of CRS. CD40-CD40L and ICOS-ICOSL signals enhance eosinophils activation of ECRS. TNF-α and IL-5 regulate eosinophils function by increasing CD40 expression partly via p38 MAPK activation in patients with CRS.
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Affiliation(s)
- Aina Zhou
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chenxi Shi
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuhui Fan
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yushuang Zheng
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jue Wang
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhichen Liu
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Huanxia Xie
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jisheng Liu
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Qingqing Jiao
- Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Chee J, Pang KW, Low T, Wang DY, Subramaniam S. Epidemiology and aetiology of chronic rhinosinusitis in Asia-A narrative review. Clin Otolaryngol 2023; 48:305-312. [PMID: 35997660 DOI: 10.1111/coa.13971] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/13/2022] [Accepted: 07/29/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Despite having a similar prevalence to Western populations, literature on chronic rhinosinusitis (CRS) in the Asian population is sparse. There is limited data on the epidemiology and aetiology of CRS in Asia. OBJECTIVES To review the current literature on the epidemiology and aetiology of CRS in Asia. METHODS This is a narrative review of published data on the epidemiology and aetiology of CRS. Studies on CRS in Asian countries, published in English and indexed on PubMed or Google Scholar were reviewed. Where available, data extracted included epidemiology, endotype and cytokine profiles and genetic profiles. RESULTS AND CONCLUSION The prevalence of CRS in Asia ranges widely from 2.1% to 28.4%. Type 2 inflammation has been reported in 5%-55% of Asian patients, with lower levels of Type 2 cytokines reported in head to head comparisons of Western versus Asian patients. Notably, there exists marked heterogeneity in criterion of the tissue eosinophilic infiltration for diagnosis of type 2 CRS. Our review suggests that differences in prevalence of CRS and proportion of eosinophilic CRS between Asia and Europe and the Americas requires further study. Large-scale Asian studies utilising standardised definitions are needed to bridge this gap. Head to head genetic and microbiomal analysis may also be useful in understanding differences in CRS between the Asian and Western populations.
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Affiliation(s)
- Jeremy Chee
- Department of Otolaryngology-Head & Neck Surgery, National University Health System, Singapore, Singapore
| | - Khang Wen Pang
- Department of Otolaryngology-Head & Neck Surgery, National University Health System, Singapore, Singapore
| | - Terese Low
- Department of Otolaryngology-Head & Neck Surgery, National University Health System, Singapore, Singapore
| | - De Yun Wang
- Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Somasundaram Subramaniam
- Department of Otolaryngology-Head & Neck Surgery, National University Health System, Singapore, Singapore
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Wang X, Sima Y, Zhao Y, Zhang N, Zheng M, Du K, Wang M, Wang Y, Hao Y, Li Y, Liu M, Piao Y, Liu C, Tomassen P, Zhang L, Bachert C. Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors. J Allergy Clin Immunol 2023; 151:458-468. [PMID: 36272582 DOI: 10.1016/j.jaci.2022.10.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 09/29/2022] [Accepted: 10/05/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Previous studies on the endotyping of chronic rhinosinusitis (CRS) that were based on inflammatory factors have broadened our understanding of the disease. However, the endotype of CRS combined with inflammatory and remodeling features has not yet been clearly elucidated. OBJECTIVE We sought to identify the endotypes of patients with CRS according to inflammatory and remodeling factors. METHODS Forty-eight inflammatory and remodeling factors in the nasal mucosal tissues of 128 CRS patients and 24 control subjects from northern China were analyzed by Luminex, ELISA, and ImmunoCAP. Sixteen factors were used to perform the cluster analysis. The characteristics of each cluster were analyzed using correlation analysis and validated by immunofluorescence staining. RESULTS Patients were classified into 5 clusters. Clusters 1 and 2 showed non-type 2 signatures with low biomarker concentrations, except for IL-19 and IL-27. Cluster 3 involved a low type 2 endotype with the highest expression of neutrophil factors, such as granulocyte colony-stimulating factor, IL-8, and myeloperoxidase, and remodeling factors, such as matrix metalloproteinases and fibronectin. Cluster 4 exhibited moderate type 2 inflammation. Cluster 5 exhibited high type 2 inflammation, which was associated with relatively higher levels of neutrophil and remodeling factors. The proportion of CRS with nasal polyps, asthma, allergies, anosmia, aspirin sensitivity, and the recurrence of CRS increased from clusters 1 to 5. CONCLUSION Diverse inflammatory mechanisms result in distinct CRS endotypes and remodeling profiles. The explicit differentiation and accurate description of these endotypes will guide targeted treatment decisions.
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Affiliation(s)
- Xiangdong Wang
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Yutong Sima
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Yan Zhao
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Nan Zhang
- Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
| | - Ming Zheng
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Kun Du
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Min Wang
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Yue Wang
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Yun Hao
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Ying Li
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | | | - Yingshi Piao
- Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Chengyao Liu
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Peter Tomassen
- Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
| | - Luo Zhang
- Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China; Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China.
| | - Claus Bachert
- Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
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Shin SH, Ye MK, Park J, Geum SY. Immunopathologic Role of Eosinophils in Eosinophilic Chronic Rhinosinusitis. Int J Mol Sci 2022; 23:ijms232113313. [PMID: 36362100 PMCID: PMC9658199 DOI: 10.3390/ijms232113313] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 10/04/2022] [Accepted: 10/29/2022] [Indexed: 11/06/2022] Open
Abstract
Chronic rhinosinusitis (CRS) is a diverse chronic inflammatory disease of the sinonasal mucosa. CRS manifests itself in a variety of clinical and immunologic patterns. The histological hallmark of eosinophilic CRS (ECRS) is eosinophil infiltration. ECRS is associated with severe disease severity, increased comorbidity, and a higher recurrence rate, as well as thick mucus production. Eosinophils play an important role in these ECRS clinical characteristics. Eosinophils are multipotential effector cells that contribute to host defense against nonphagocytable pathogens, as well as allergic and nonallergic inflammatory diseases. Eosinophils interact with Staphylococcus aureus, Staphylococcal enterotoxin B, and fungi, all of which were found in the tissue of CRS patients. These interactions activate Th2 immune responses in the sinonasal mucosa and exacerbate local inflammation. Activated eosinophils were discovered not only in the tissue but also in the sinonasal cavity secretion. Eosinophil extracellular traps (EETs) are extracellular microbes trapping and killing structures found in the secretions of CRS patients with intact granule protein and filamentous chromatic structures. At the same time, EET has a negative effect by causing an epithelial barrier defect. Eosinophils also influence the local tissue microenvironment by exchanging signals with other immune cells and structural cells. As a result, eosinophils are multifaceted leukocytes that contribute to various physiologic and pathologic processes of the upper respiratory mucosal immune system. The goal of this review is to summarize recent research on the immunopathologic properties and immunologic role of eosinophils in CRS.
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Xu S, Vallei M, Hwang Siok Gek J, Tze Choong C, Wei Yang Teo N. Endotyping of nasal polyps in a multiracial Asian population. RHINOLOGY ONLINE 2022. [DOI: 10.4193/rhinol/22.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background: Chronic rhinosinusitis is a heterogenous disease with variation in the endotypes of nasal polyps, with type 2 inflammation being more prevalent in Caucasian populations whereas Chinese populations are more heterogenous. We aim to describe the variation in endotypes for patients with chronic rhinosinusitis with nasal polyposis in our unique multiracial population. Methodology: Demographic, clinical and structured histopathological data of 66 patients who underwent sinus surgery for nasal polyposis were evaluated retrospectively. Results: 54.6% had eosinophilic disease, and 45.4% had non-eosinophilic disease with no significant demographic differences between the 2 populations. There were significantly higher peripheral eosinophil levels in patients with eosinophil-predominant inflammation on tissue histology (mean absolute eosinophil count 0.59 ± 0.18 x 109) compared with non-eosinophilic disease (mean absolute eosinophil count 0.24 ± 0.11 x 109). Structured histopathological reporting revealed that patients with eosinophilic disease had higher degree of inflammation and eosinophil aggregates. Conclusions: Our population is shown to have a slight preponderance toward eosinophilic disease, however the Chinese majority tended to have non-eosinophilic disease. Serum eosinophilia and the presence of asthma seems to correlate well with tissue eosinophilia, which can potentially be utilised as markers of type 2 inflammatory disease.
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14
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Lin L, Lan J, Dai F, Wei J, Chen Z. Effect of Local Corticosteroid Administration on CD8+CD25+Foxp3+ Tregs in Neutrophilic CRSwNP. ORL J Otorhinolaryngol Relat Spec 2022; 84:396-405. [PMID: 35468610 DOI: 10.1159/000524385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 03/26/2022] [Indexed: 02/05/2023]
Abstract
INTRODUCTION CD8+CD25+Foxp3+ regulatory T cells (Tregs) play an important role in human's immune tolerance. The study was aimed to assess the influence of budesonide nasal spray on CD8+CD25+Foxp3+ Tregs and to evaluate their cellular functions in neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNPs). METHODS Fifteen patients with neutrophilic CRSwNPs were enrolled and received physiological saline or budesonide nasal spray treatment (Saline or Budesonide group) for 3 months. Nasal tissue samples were obtained from normal subjects or those patients and cultured in vitro. CD8+CD25+Foxp3+ Tregs were separated from normal or NP tissues and also cultured in vitro. Then interleukin (IL)-10 and its mRNA were evaluated in the above cell cultures. The cells were applied into NP cultures. Finally, myeloperoxidase (MPO), interferon (IFN)-γ, IL-1β, and tumor necrosis factor (TNF)-α were assessed in the tissue cultures. RESULTS CD8+CD25+Foxp3+ Tregs decreased in NP tissues. Budesonide administration did not enhance the percentage of these cells in polypoid tissues. IL-10 and its mRNA were increased in the above cell cultures from NPs. However, there were no statistical differences between the two treatments in the IL-10 expression. Additionally, levels of MPO, IFN-γ, IL-1β, and TNF-α were totally elevated in NP tissue cultures and reduced after the administration of CD8+CD25+Foxp3+ Tregs. However, there were no significant differences in concentrations of these mediators between these two groups of the CD8+CD25+Foxp3+ Tregs treatment in vitro. CONCLUSION The findings indicate that CD8+CD25+Foxp3+ Tregs might regulate the neutrophilic inflammation, and budesonide nasal spray therapy could not ameliorate the inflammation in neutrophilic CRSwNPs.
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Affiliation(s)
- Lin Lin
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China
| | - Jing Lan
- Department of Gynecology and Obstetrics, Huashan Hospital North of Fudan University, Shanghai, China
| | - Fei Dai
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China
| | - Jinjin Wei
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China
| | - Zheng Chen
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China
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15
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Yao Y, Zeng M, Liu Z. Revisiting Asian chronic rhinosinusitis in the era of type 2 biologics. Clin Exp Allergy 2021; 52:231-243. [PMID: 34854144 DOI: 10.1111/cea.14065] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/25/2021] [Accepted: 11/27/2021] [Indexed: 01/08/2023]
Abstract
Chronic rhinosinusitis (CRS) is a highly heterogeneous disorder exhibiting considerable epidemiological, clinical and immunopathological variations across patients with distinct ethnic backgrounds and in different geographic locations. Asian CRS patients present less eosinophilic and type 2 (T2) inflammation, but more prominent neutrophilic inflammation compared with patients in Western countries. Although several biologics targeting important elements of T2 inflammation, such as IL-4, IL-5, IL-13 and IgE, demonstrate promising benefit for Caucasian patients with recurrent nasal polyps, their efficacy in Asian patients remains poorly defined. The distinct endotypes in Asian patients warrant the identification and selection of patients who would benefit from T2 biologics in Asian countries. Additionally, developing novel treatments targeting neutrophilic, type 1, and type 3 inflammation may benefit approximately 50% of Asian CRS patients with non-T2 inflammation. In this review, we summarized and discussed recent progress in the study of Asian CRS endotypes in comparison with those in patients in Western countries, and the methods of identifying Asian patients with eosinophilic or T2 inflammation. T2 biologic treatment of Asian CRS patients, potential therapeutic candidates targeting non-T2 inflammation in Asian CRS patients and the progress on developing other T2 biologics were discussed.
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Affiliation(s)
- Yin Yao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ming Zeng
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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16
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Nakayama T, Lee IT, Le W, Tsunemi Y, Borchard NA, Zarabanda D, Dholakia SS, Gall PA, Yang A, Kim D, Akutsu M, Kashiwagi T, Patel ZM, Hwang PH, Frank DN, Haruna SI, Ramakrishnan VR, Nolan GP, Jiang S, Nayak JV. Inflammatory molecular endotypes of nasal polyps derived from Caucasian and Japanese populations. J Allergy Clin Immunol 2021; 149:1296-1308.e6. [PMID: 34863854 DOI: 10.1016/j.jaci.2021.11.017] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 11/10/2021] [Accepted: 11/17/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Little is known currently about possible distinguishing factors underlying these inflammatory differences. OBJECTIVE To interrogate for differences between Caucasian and Japanese CRSwNP disease using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs). METHODS We performed whole transcriptome RNA sequencing (RNA-seq) with endotype stratification of NPs from 8 Caucasian (residing in USA) and 9 Japanese (residing in Japan) patients. Reproducibility was confirmed by qPCR in an independent validation set of 46 Caucasian and 31 Japanese patients. Single-cell RNA-seq stratified key cell types for contributory transcriptional signatures. RESULTS Unsupervised clustering analysis identified two major endotypes present within both NP cohorts, which have previously been reported at the cytokine level: 1) type 2 endotype and 2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct NP subgroups (p = 0.03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells. CONCLUSION NPs from both racial groups harbor the same two major endotypes, which we determine are present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed.
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Affiliation(s)
- Tsuguhisa Nakayama
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA; Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan
| | - Ivan T Lee
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
| | - Wei Le
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Yasuhiro Tsunemi
- Department of Otorhinolaryngology-Head and Neck Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Nicole A Borchard
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - David Zarabanda
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Sachi S Dholakia
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Philip A Gall
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Angela Yang
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Dayoung Kim
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Makoto Akutsu
- Department of Otorhinolaryngology-Head and Neck Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Takashi Kashiwagi
- Department of Otorhinolaryngology-Head and Neck Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Zara M Patel
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Peter H Hwang
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Daniel N Frank
- Division of Infectious Diseases, University of Colorado, Aurora, CO, USA
| | - Shin-Ichi Haruna
- Department of Otorhinolaryngology-Head and Neck Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Vijay R Ramakrishnan
- Department of Otolaryngology-Head and Neck Surgery, University of Colorado, Aurora, CO, USA
| | - Garry P Nolan
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Sizun Jiang
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
| | - Jayakar V Nayak
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA; Department of Otolaryngology-Head and Neck Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
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Yu J, Xian M, Piao Y, Zhang L, Wang C. Changes in Clinical and Histological Characteristics of Nasal Polyps in Northern China over the Past 2-3 Decades. Int Arch Allergy Immunol 2021; 182:615-624. [PMID: 33596581 DOI: 10.1159/000513312] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 11/23/2020] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION Recent studies have shown that inflammatory patterns of nasal polyps from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) in East Asia have changed over time. However, to date there is a marked lack of similar data for CRSwNP in Northern China. This study thus aimed to assess the changes in the clinical and histological characteristics of CRSwNP patients from Northern China over the past 2-3 decades. METHODS This was a retrospective study, which examined data from 2 groups of 150 CRSwNP patients each, who had undergone endoscopic sinus surgery in Beijing Tongren Hospital from 1993 to 1995 (group A) and from 2015 to 2019 (group B). All relevant data for demographic, clinical, and histological parameters were collected for each patient from the 2 groups and compared for overall changes between the 2 groups. RESULTS The comorbidity of CRSwNP and asthma increased over time and the cellular phenotype of CRSwNPchanged significantly; in particular, the proportion of eosinophil-dominant CRSwNP increased, lymphocyte-dominant and plasma-dominant CRSwNP decreased significantly, and the proportions of neutrophil-dominant and mixed CRSwNP were not altered. The rate of polyp recurrence increased in CRSwNP but did not in eosinophilic CRSwNP. Smoking and age did not significantly impact the inflammatory patterns of CRSwNP. CONCLUSIONS The inflammatory patterns of CRSwNP patients have changed and comorbidity of asthma significantly increased in CRSwNP patients in Northern China over the past 2-3 decades.
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Affiliation(s)
- Jiaqi Yu
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Mu Xian
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Yingshi Piao
- Department of Pathology, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Luo Zhang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China, .,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China, .,Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China, .,Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China,
| | - Chengshuo Wang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.,Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
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18
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Perić A, Vukomanović Đurđević B. Nasal polyp epithelial atypia and exposure to nickel and copper. Occup Med (Lond) 2020; 70:72-74. [PMID: 31587045 DOI: 10.1093/occmed/kqz123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Possible factors for cell atypia in nasal mucosa include noxious chemicals: ammonia, formaldehyde and heavy metals. AIMS Case presentation of a nasal polyp with epithelial dysplasia in a worker exposed to nickel and copper salt dust. CASE REPORT A 27-year-old man complained of impaired nasal breathing and mild right-sided epistaxis. He was exposed to copper and nickel salt dust for 6 years. Clinical examination showed a polypoid lesion arising from the right middle turbinate. Histopathological examination of the excised lesion showed high-grade epithelial dysplasia. Duration of exposure and concentration of heavy metals in serum suggest the biological plausibility of exposure to these factors and development of epithelial dysplasia in the nasal mucosa. CONCLUSIONS Epithelial dysplasia may occasionally be noted in inflammatory nasal polyps, especially in workers exposed to heavy metals.
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Affiliation(s)
- A Perić
- Department of Otorhinolaryngology, Military Medical Academy Faculty of Medicine, Crnotravska, Belgrade, Serbia
| | - B Vukomanović Đurđević
- Institute for Pathology, Military Medical Academy Faculty of Medicine, Crnotravska, Belgrade, Serbia
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Fadda GL, Galizia A, Galizia G, Castelnuovo P, Bignami M, Cavallo G. Multiparametric Analysis of Factors Associated With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps. EAR, NOSE & THROAT JOURNAL 2020; 101:NP256-NP262. [PMID: 33023335 DOI: 10.1177/0145561320960357] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Previous studies have reported a diverse range of threshold values for blood eosinophilia. In addition, a single predictive biomarker for eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (ECRSwNP) has not yet been identified. OBJECTIVES The aim of this study is to compare the clinical characteristics of ECRSwNP and non-ECRSwNP to evaluate the preoperative risk of tissue eosinophilia of chronic rhinosinusitis with nasal polyps (CRSwNP) through a multiparametric statistical analysis. METHODS One hundred ten patients with evidence of chronic polypoid rhinosinusitis were included in this study and clinical records were retrospectively reviewed. Eosinophilic CRSwNP was diagnosed based on the presence of at least 10 eosinophils per high-power field. The demographic and clinical features of ECRSwNP and non-ECRSwNP are described. The values of blood eosinophilia as predictors of tissue eosinophilia have been identified using receiver operating characteristic curves. As the predictive value of the identified cutoff through regression analysis was low, we evaluated whether other risk factors could be statistically associated with ECRSwNP, and from this, a new predictive model was proposed for the identification of eosinophilic nasal polyps before surgery. RESULTS We found that the best method for predicting ECRSwNP is based on a model having asthma, blood eosinophil percentage, posterior ethmoid value in Lund-Mackay score, and modified Lund-Kennedy score as explanatory variables. CONCLUSIONS This study provides new data for a better understanding of the polypoid CRS endotypes, and the proposed model allows the endotype to be identified preoperatively.
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Affiliation(s)
- Gian Luca Fadda
- Department of Otorhinolaryngology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Andrea Galizia
- Department of Otorhinolaryngology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Giuseppe Galizia
- Department of Otorhinolaryngology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Paolo Castelnuovo
- Department of Otorhinolaryngology, University of Insubria, Varese, Italy
| | - Maurizio Bignami
- Department of Otorhinolaryngology, University of Insubria, Varese, Italy
| | - Giovanni Cavallo
- Department of Otorhinolaryngology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy
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Karin J, Tim D, Gabriele H, Cardell LO, Marit W, Claus B. Type 2 Inflammatory Shift in Chronic Rhinosinusitis During 2007-2018 in Belgium. Laryngoscope 2020; 131:E1408-E1414. [PMID: 32965716 DOI: 10.1002/lary.29128] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 08/25/2020] [Accepted: 08/29/2020] [Indexed: 01/22/2023]
Abstract
OBJECTIVES/HYPOTHESIS Chronic rhinosinusitis (CRS) is a heterogenic disease with different inflammatory patterns depending on the presence (CRSwNP) or absence (CRSsNP) of polyps and geographical location. A shift toward type 2 endotype has been seen in Asia. We aim to investigate whether there has been type 2 shift in Belgium and to further endotype CRS based on clinical markers. STUDY DESIGN Prospective descriptive study. METHODS Four hundred and thirty eight patients with CRS undergoing sinus surgery at Ghent University Hospital between 2007 and 2018 were included and stratified based on phenotype, comorbidities, inflammatory markers in tissue, and two different time points of surgery. Tissue samples from surgery were analyzed for type 2 markers. In a subgroup of CRSwNP blood eosinophils (EBC) was available. RESULTS There was an increase in type 2 inflammatory markers in the latter group versus the earlier, in non-asthmatic, non-allergic CRS patients regardless of phenotype. The proportion of IL-5+ patients was elevated in the latter group in CRSwNP. Inflammatory markers and comorbidities differ between IL-5+ CRSsNP and CRSwNP subjects, no difference was seen in IL-5- CRS. EBC can together with information on comorbidities help identify type 2 CRSwNP in a clinical setting. CONCLUSION There is a shift toward type 2 inflammation within the CRS population over recent 8 years also in Belgium. This shift implies that we expect to see more cases of severe and difficult to treat CRS in the future. Polyp formation is not directly linked to the presence or concentrations of type 2 inflammatory markers. Clinical parameters and EBC > 300 cells/μL can be used to identify type 2 CRSwNP. LEVEL OF EVIDENCE 3. Laryngoscope, 131:E1408-E1414, 2021.
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Affiliation(s)
- Jonstam Karin
- Department of Clinical Science, Intervention and Technology, Division of Ear, Nose and Throat Diseases, Karolinska Institutet, Stockholm, Sweden.,Department of Ear, Nose and Throat Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Delemarre Tim
- Upper Airway Research Laboratory, Ghent University, Ghent, Belgium
| | | | - Lars-Olaf Cardell
- Department of Clinical Science, Intervention and Technology, Division of Ear, Nose and Throat Diseases, Karolinska Institutet, Stockholm, Sweden.,Department of Ear, Nose and Throat Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Westman Marit
- Department of Ear, Nose and Throat Diseases, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Bachert Claus
- Department of Clinical Science, Intervention and Technology, Division of Ear, Nose and Throat Diseases, Karolinska Institutet, Stockholm, Sweden.,Department of Ear, Nose and Throat Diseases, Karolinska University Hospital, Stockholm, Sweden.,Upper Airway Research Laboratory, Ghent University, Ghent, Belgium
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21
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Kanemitsu Y, Kurokawa R, Ono J, Fukumitsu K, Takeda N, Fukuda S, Uemura T, Tajiri T, Ohkubo H, Maeno K, Ito Y, Oguri T, Takemura M, Yap J, Nishiyama H, Masaki A, Ozawa Y, Izuhara K, Suzuki M, Niimi A. Increased Serum Periostin Levels and Eosinophils in Nasal Polyps Are Associated with the Preventive Effect of Endoscopic Sinus Surgery for Asthma Exacerbations in Chronic Rhinosinusitis Patients. Int Arch Allergy Immunol 2020; 181:862-870. [PMID: 32731246 DOI: 10.1159/000509253] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 06/08/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Eosinophilic nasal polyps (NPs) are associated with the presence of asthma in chronic rhinosinusitis (CRS) patients. Serum periostin has been considered a relevant biomarker for unified airway diseases. OBJECTIVE To determine the utility of biomarkers including serum periostin that reflects reduction of exacerbations of comorbid asthma in CRS patients. METHODS We prospectively recruited 56 CRS patients who were subjected to undergo endoscopic sinus surgery (ESS) (20 with asthma) between October 2015 and December 2017 and followed them for 1 year after ESS. Blood eosinophil count, serum periostin, and fractional nitric oxide (FeNO) were measured at enrollment. How these type 2-driven biomarkers reflect comorbid asthma was determined using receiver operating characteristic (ROC) analysis. The frequency of asthma exacerbations during 1 year was counted both before and after ESS. Associations between preoperative biomarkers including eosinophils in NPs and asthma exacerbations were evaluated. RESULTS Blood eosinophil count, FeNO, and serum periostin levels were significantly higher in CRS patients with asthma than in those without (p < 0.01 for all) and discriminated comorbid asthma among CRS patients (p < 0.05; AUC > 0.80 for all). The increased preoperative serum periostin correlated with lower absolute number of postoperative exacerbations (ρ = -0.49, p = 0.03) and its relative reduction after ESS (ρ = 0.53, p = 0.03) in asthmatic patients. Increased eosinophils in NPs were also associated with reduced asthma exacerbations. CONCLUSION Preoperative increased serum periostin and eosinophils in NPs are associated with the preventive effect of ESS for asthma exacerbations in CRS patients comorbid with asthma.
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Affiliation(s)
- Yoshihiro Kanemitsu
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan,
| | - Ryota Kurokawa
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Junya Ono
- Shino-Test Corporation, Sagamihara, Japan
| | - Kensuke Fukumitsu
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Norihisa Takeda
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Satoshi Fukuda
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takehiro Uemura
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Tomoko Tajiri
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hirotsugu Ohkubo
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Ken Maeno
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yutaka Ito
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Tetsuya Oguri
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Masaya Takemura
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Jennifer Yap
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hirono Nishiyama
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Ayako Masaki
- Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yoshiyuki Ozawa
- Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kenji Izuhara
- The Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan
| | - Motohiko Suzuki
- Department of Otorhinolaryngology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Akio Niimi
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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22
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Liu Z, Chen J, Cheng L, Li H, Liu S, Lou H, Shi J, Sun Y, Wang D, Wang C, Wang X, Wei Y, Wen W, Yang P, Yang Q, Zhang G, Zhang Y, Zhao C, Zhu D, Zhu L, Chen F, Dong Y, Fu Q, Li J, Li Y, Liu C, Liu F, Lu M, Meng Y, Sha J, She W, Shi L, Wang K, Xue J, Yang L, Yin M, Zhang L, Zheng M, Zhou B, Zhang L. Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2020; 12:176-237. [PMID: 32009319 PMCID: PMC6997287 DOI: 10.4168/aair.2020.12.2.176] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 11/05/2019] [Accepted: 11/13/2019] [Indexed: 02/05/2023]
Abstract
The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines-with a focus on China-will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
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Affiliation(s)
- Zheng Liu
- Department of Otolaryngology Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jianjun Chen
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Cheng
- Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
- International Centre for Allergy Research, Nanjing Medical University, Nanjing, China
| | - Huabin Li
- Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China
| | - Shixi Liu
- Department of Otolaryngology, West China Hospital, Sichuan University, Chengdu, China
| | - Hongfei Lou
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Jianbo Shi
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ying Sun
- Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Dehui Wang
- Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China
| | - Chengshuo Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Xiangdong Wang
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Yongxiang Wei
- Department of Otolaryngology Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Weiping Wen
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Otorhinolaryngology Hospital, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Pingchang Yang
- Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China
| | - Qintai Yang
- Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Gehua Zhang
- Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuan Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Changqing Zhao
- Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Shanxi Medical University, Taiyuan, China
| | - Dongdong Zhu
- Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Li Zhu
- Department of Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, China
| | - Fenghong Chen
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yi Dong
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Qingling Fu
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jingyun Li
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Yanqing Li
- Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China
| | - Chengyao Liu
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Feng Liu
- Department of Otolaryngology, West China Hospital, Sichuan University, Chengdu, China
| | - Meiping Lu
- Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Yifan Meng
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Jichao Sha
- Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Wenyu She
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Lili Shi
- Department of Otolaryngology Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kuiji Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Jinmei Xue
- Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Shanxi Medical University, Taiyuan, China
| | - Luoying Yang
- Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Min Yin
- Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
- International Centre for Allergy Research, Nanjing Medical University, Nanjing, China
| | - Lichuan Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Ming Zheng
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Bing Zhou
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
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23
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Xu Q, Du K, Zheng M, Duan S, Jia S, Chen H, Wang X, Zhang L. Application of Clinical Scores in the Differential Diagnosis of Chronic Rhinosinusitis With Nasal Polyps in a Chinese Population. Am J Rhinol Allergy 2020; 34:401-408. [PMID: 31992047 DOI: 10.1177/1945892420901996] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background Eosinophilic (Eos) and non-eosinophilic (non-Eos) chronic rhinosinusitis with nasal polyps (CRSwNP) react differently to clinical treatment, with eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) being more likely to recur after surgery. Objective To explore the clinical value of the visual analog scale (VAS), nasal endoscopy score (Lund–Kennedy, L–K), computed tomography (CT) score (Lund–Mackay scoring system, L–M), and blood Eos percentage in the differential diagnosis of Eos CRSwNP and non-Eos CRSwNP. Methods Ninety-nine patients with CRSwNP were enrolled in this study and assigned to 2 groups (Eos CRSwNP and non-Eos CRSwNP). The blood Eos percentage and VAS, L–K, and L–M scores in the 2 groups of patients were compared. A receiver operating characteristic (ROC) was used to assess the usefulness of VAS, L–K, and L–M scores for differentiating Eos CRSwNP and non-Eos CRSwNP. Results There were significantly differences between the Eos CRSwNP group and non-Eos CRSwNP group in the following scores: blood Eos percentage, mean VAS score, olfaction/VAS, general discomfort/L–K, edema score/L–K, olfactory cleft (OC) score via endoscopy, mean L–M score, anteriorethmoid sinus score, posterior ethmoid sinus score, sphenoid sinus score, frontal sinus score, and OC score via CT. An ROC analysis showed that blood Eos percentage had the highest area under the ROC curve (AUC) value (0.749); however, several other scores (olfaction score/VAS, edema score/L–K, and mean L–M score) also had high AUC values. The combination of olfaction score/VAS and blood Eos percentage had the highest clinical convenience score as well as high sensitivity and specificity. A combination of cutoff values for the 2 predictors (blood Eos percentage ≥3.85%, olfaction score/VAS score ≥3) showed a sensitivity of 75.5% and a specificity of 78.0%. Conclusion The olfaction score/VAS score and the blood Eos percentage can be combined to differentiate Eos CRSwNP from non-Eos CRSwNP in a Chinese population.
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Affiliation(s)
- Qingqing Xu
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Kun Du
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Ming Zheng
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Su Duan
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Shuangshuang Jia
- Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Hui Chen
- Department of Otolaryngology, Wang Jing Hospital of CACMS, Beijing, PR China
| | - Xiangdong Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
| | - Luo Zhang
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
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Lou H, Wang C, Zhang L. Endotype-driven precision medicine in chronic rhinosinusitis. Expert Rev Clin Immunol 2019; 15:1171-1183. [PMID: 31600458 DOI: 10.1080/1744666x.2020.1679626] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Hongfei Lou
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Chengshuo Wang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Luo Zhang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China
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25
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Song WJ, Lee JH, Won HK, Bachert C. Chronic Rhinosinusitis with Nasal Polyps in Older Adults: Clinical Presentation, Pathophysiology, and Comorbidity. Curr Allergy Asthma Rep 2019; 19:46. [PMID: 31486905 DOI: 10.1007/s11882-019-0880-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Chronic rhinosinusitis and nasal polyps (CRSwNP) is a common condition that significantly affects patients' life. This work aims to provide an up-to-date overview of CRSwNP in older adults, focusing on its aging-related clinical presentations, pathophysiology, and comorbidity associations including asthma. RECENT FINDINGS Recent large population-based studies using nasal endoscopy have shown that CRSwNP is a mostly late-onset disease. Age-related changes in physiologic functions, including nasal epithelial barrier dysfunction, may underlie the incidence and different clinical presentations of CRSwNP in older adults. However, there is still a paucity of evidence on the effect of aging on phenotypes and endotypes of CRSwNP. Meanwhile, late-onset asthma is a major comorbid condition in patients with CRSwNP; they frequently present with type 2 inflammatory signatures that are refractory to conventional treatments when they are comorbid. However, as they are more commonly non-atopic, causative factors other than classical atopic sensitization, such as Staphylococcus aureus specific IgE sensitization, are suggested to drive the type 2 inflammation. There are additional comorbidity associations in older patients with CRSwNP, including those with chronic otitis media and head and neck malignancy. Age is a major determinant for the incidence and clinical presentations of CRSwNP. Given the heterogeneity in phenotypes and endotypes, longitudinal investigations are warranted to elucidate the effects of aging on CRSwNP.
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Affiliation(s)
- Woo-Jung Song
- Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
| | - Ji-Hyang Lee
- Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Ha-Kyeong Won
- Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, South Korea
| | - Claus Bachert
- Upper Airways Research Laboratory, Ghent University Hospital, Ghent, Belgium
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Perić A, Stoiljkov M, Đokić D, Đurđević BV. Epithelial Squamous Metaplasia and Dysplasia in Inflammatory Nasal Polyps: An Observational Study. EAR, NOSE & THROAT JOURNAL 2019; 100:NP120-NP124. [PMID: 31309847 DOI: 10.1177/0145561319862207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Nasal polyposis (NP) is characterized by polypoid outgrowths of chronically inflamed respiratory mucosa. The presence of squamous metaplasia and dysplasia on the mucosal surface of nasal polyps (NPs) represents different manifestations of epithelial atypia. The aim of this investigation was to evaluate the presence of epithelial squamous metaplasia and dysplasia in ethmoidal NPs. This retrospective analysis of prospectively collected data involved 212 patients with NP undergoing endoscopic ethmoidectomy. To evaluate possible etiological factors for epithelial atypia, the patients in whom we histopathologically detected the presence of epithelial atypia were compared with patients with "normal" NPs in accordance with the following characteristics as found in the patients' medical records: gender, age, main symptoms, preoperative extent of sinus disease on computed tomography, atopic status, aspirin sensitivity, cigarette smoking, and occupational exposure to different noxious factors. Epithelial atypia were detected histopathologically in 44 (20.7%) NP patients, whereas features of "true" dysplasia were found in only 1 (0.5%) patient. The presence of atypia was more frequent in males than in females (P = .008). The association with aspirin-exacerbated respiratory disease and with long-term occupational exposure to different noxious chemicals, especially in workers exposed to salts of heavy metals, was more frequent in NP patients with epithelial atypia than in patients without atypia (P = .023; P = .006, respectively). Our results suggest epithelial atypia in NPs are associated with aspirin sensitivity and occupational exposure to different noxious chemicals. Although extremely rare, epithelial dysplasia may occasionally be noted in NPs, a fact potentially useful for both rhinologists and pathologists.
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Affiliation(s)
- Aleksandar Perić
- Department of Otorhinolaryngology, Military Medical Academy Faculty of Medicine, Belgrade, Serbia
| | - Marko Stoiljkov
- Department of Otorhinolaryngology, Military Medical Academy Faculty of Medicine, Belgrade, Serbia.,ENT Unit, General Hospital Bar, Bar, Montenegro
| | - Danijela Đokić
- Department of Otorhinolaryngology, Military Medical Academy Faculty of Medicine, Belgrade, Serbia
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27
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Wang M, Zhang N, Zheng M, Li Y, Meng L, Ruan Y, Han J, Zhao N, Wang X, Zhang L, Bachert C. Cross-talk between T H2 and T H17 pathways in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 2019; 144:1254-1264. [PMID: 31271788 DOI: 10.1016/j.jaci.2019.06.023] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 06/10/2019] [Accepted: 06/14/2019] [Indexed: 11/28/2022]
Abstract
BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a spectrum of endotypes. TH2- and TH17-related cytokines are 2 central regulators involved in the inflammation associated with CRSwNP. OBJECTIVE We sought to investigate the interregulation of TH2 and TH17 pathways in Chinese patients with CRSwNP. METHODS Levels of key TH2- and TH17-related factors were measured in homogenates of polyp tissue obtained from patients with CRSwNP. The relationship of these factors and their expression in groups classified according to tissue IL-5 and IL-17 concentrations were analyzed. Cross-regulation of TH2 and TH17 cytokines and the effects of dexamethasone treatment were studied in dispersed nasal polyp cells. Associations between TH2- and TH17 related factors and comorbid atopic status and asthma, disease recurrence, and edema scores were also explored. RESULTS Four CRSwNP groups were classified based on expression or nonexpression of mutually exclusive TH2- and TH17-related factors. The TH2 cytokines IL-4 and IL-13 inhibited expression of TH17-related factors, whereas the TH17 cytokines IL-17 and TGF-β1 enhanced expression of TH2-related factors. Dexamethasone treatment inhibited both the TH2 and TH17 pathways. A patient's atopic status was related to their TH2 immune response. Edema scores were positively correlated with the TH2 pathway and negatively correlated with the TH17 pathway. CONCLUSION The TH2 and TH17 pathways are mutually exclusive and regulate each other, favoring the development of a TH2 immune response in Chinese patients with CRSwNP.
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Affiliation(s)
- Min Wang
- Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Nan Zhang
- Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
| | - Ming Zheng
- Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Ying Li
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Lingling Meng
- Department of Otolaryngology, Bayan Nur Hospital, Bayan Nur, China
| | - Yu Ruan
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Jinbo Han
- Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Na Zhao
- Department of Otolaryngology, Yanqing District Hospital, General Practice and Continuing Education Capital Medical University, Beijing, China
| | - Xiangdong Wang
- Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China; Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
| | - Luo Zhang
- Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China; Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
| | - Claus Bachert
- Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium; Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Stockholm, Sweden; Department of Ear, Nose and Throat Diseases, Karolinska University Hospital, Stockholm, Sweden
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Predictors of disease progression after endoscopic sinus surgery in patients with chronic rhinosinusitis. The Journal of Laryngology & Otology 2019; 133:678-684. [PMID: 31218991 DOI: 10.1017/s0022215119001245] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE This study aimed to determine the predictors of disease progression after functional endoscopic sinus surgery in patients with chronic rhinosinusitis. METHOD A total of 281 adult chronic rhinosinusitis patients who underwent primary bilateral functional endoscopic sinus surgery between 2007 and 2017 and had at least 12 months of follow-up endoscopic evaluation were examined. Patients were divided into eosinophilic (n = 205) and non-eosinophilic chronic rhinosinusitis groups (n = 76). In order to determine adverse factors, post-operative endoscopic appearance scores were analysed in relation to the pre- and intra-operative findings using multiple regression analyses. RESULTS The post-operative course of eosinophilic cases deteriorated over time, like the early period for non-eosinophilic cases. Frontal sinus polyps recurred early in eosinophilic chronic rhinosinusitis. Multivariate analyses indicated young adulthood, asthma, high computed tomography score and frontal sinus polyps as significant adverse predictors. CONCLUSION Early, appropriate estimation of sinonasal conditions appears to be crucial for successful surgical management of chronic rhinosinusitis.
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Pezato R, Voegels RL, Pignatari S, Gregório LC, Pinto Bezerra TF, Gregorio L, Balsalobre L, Tepedino MS, Coronel N, Pinna FDR, Mendes Neto J, Oliveira P, Macoto E, Stefanini R, Figueiredo C, Haddad F, Pilan R, Bezerra Soter A, Melo NA, Candido DA, Amaral JD, Santos RDP, Van Zele T, Fujita R, Dreyfuss JL, Chamon W, Alencar AM, Perez-Novo C, Stamm AC. Nasal Polyposis: More than a Chronic Inflammatory Disorder-A Disease of Mechanical Dysfunction-The São Paulo Position. Int Arch Otorhinolaryngol 2019; 23:241-249. [PMID: 30956711 PMCID: PMC6449132 DOI: 10.1055/s-0038-1676659] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 10/21/2018] [Indexed: 01/02/2023] Open
Abstract
Introduction The importance of our study lies in the fact that we have demonstrated the occurrence of mechanical dysfunction within polypoid tissues, which promotes the development of polyps in the nasal cavity. Objective To change the paradigm of nasal polyposis (NP). In this new conception, the chronic nasal inflammatory process that occurs in response to allergies, to pollution, to changes in the epithelial barrier, or to other factors is merely the trigger of the development of the disease in individuals with a genetic predisposition to an abnormal tissue remodeling process, which leads to a derangement of the mechanical properties of the nasal mucosa and, consequently, allows it to grow unchecked. Data Synthesis We propose a fundamentally new approach to intervening in the pathological process of NP, addressing biomechanical properties, fluid dynamics, and the concept of surface tension. Conclusion The incorporation of biomechanical knowledge into our understanding of NP provides a new perspective to help elucidate the physiology and the pathology of nasal polyps, and new avenues for the treatment and cure of NP.
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Affiliation(s)
- Rogerio Pezato
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | | | - Shirley Pignatari
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | - Luiz Carlos Gregório
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | | | - Luciano Gregorio
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | - Leonardo Balsalobre
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | | | - Nathália Coronel
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | | | - José Mendes Neto
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | - Pedro Oliveira
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | - Eduardo Macoto
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | - Renato Stefanini
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | - Claudia Figueiredo
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | - Fernanda Haddad
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | - Renata Pilan
- Department of Otolaryngology, USP, São Paulo, SP, Brazil
| | | | | | | | - Jonatas do Amaral
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | | | - Thibaut Van Zele
- Ear, Nose and Throat Department,, University of Ghent, Ghent, Belgium
| | - Reginaldo Fujita
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
| | | | - Wallace Chamon
- Department of Ophthalmology and Visual Sciences, Unifesp, São Paulo, SP, Brazil
- Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Adriano Mesquita Alencar
- Laboratory of Microrheology and Molecular Physiology, Institute of Physics, USP, São Paulo, SP, Brazil
| | - Claudina Perez-Novo
- Proteinscience, Proteomics and Epigenetic Signaling, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Aldo Cassol Stamm
- Department of Otolaryngology – Head and Neck Surgery, Unifesp, São Paulo, SP, Brazil
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Regulation of Interaction between the Upper and Lower Airways in United Airway Disease. Med Sci (Basel) 2019; 7:medsci7020027. [PMID: 30754692 PMCID: PMC6410259 DOI: 10.3390/medsci7020027] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 02/08/2019] [Accepted: 02/08/2019] [Indexed: 01/29/2023] Open
Abstract
The concept of united airway disease comprises allergic rhinitis (AR) with asthma, and eosinophilic chronic rhinosinusitis (ECRS) with asthma. It embodies a comprehensive approach to the treatment of upper and lower airway inflammation. The treatment of upper airway inflammation reduces asthma symptoms and decreases the dose of inhaled corticosteroids (ICS) necessary to treat asthma. However, little is known about the mechanisms of interaction between upper and lower airway inflammation. Here we review these mechanisms, focusing on neural modulation and introduce a novel therapeutic approach to united airway disease using a fine-particle ICS. Our understanding of the relationship between the upper and lower airways and its contribution to T helper 2 (Th2)-skewed disease, such as AR and/or ECRS with asthma, has led us to this novel therapeutic strategy for a comprehensive approach to the treatment of upper airway inflammation with asthma.
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Zheng R, Wang D, Wang K, Gao WX, Yang QT, Jiang LJ, Zhou M, Cao YJ, Shi J, Sun Y. Elevated expression of IL-17RB and ST2 on myeloid dendritic cells is associated with a Th2-skewed eosinophilic inflammation in nasal polyps. Clin Transl Allergy 2018; 8:50. [PMID: 30519393 PMCID: PMC6263180 DOI: 10.1186/s13601-018-0237-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 11/16/2018] [Indexed: 12/19/2022] Open
Abstract
Background Interleukin(IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) underlie the crosstalk between epithelial cells and dendritic cells (DCs) during the development of Th2 responses. This study aimed to measure the expressions of IL-17RB, ST2 and TSLPR, receptor of IL-25, IL-33, and TSLP respectively, on myeloid DCs in nasal polyps (NP) and evaluate their association with local Th2 inflammation and disease severity in patients with NP. Methods Samples were collected from 30 NP patients and 16 control subjects recruited prospectively. The mRNA expression of cytokines, including TSLP, IL-25 and IL-33, as well as interferon (IFN)-γ, IL-4, IL-5, IL-13 and IL-17A in NP and control tissues was examined by qualitative polymerase chain reaction (qPCR). The expression of IL-17RB, ST2 and TSLPR as well as other surface markers on myeloid DCs (mDCs) was examined by flow cytometry. Results Increased numbers of total and activated mDCs were found in NP patients. mDCs demonstrated significantly higher expression of IL-17RB, ST2 and TSLPR than those in control tissues. The activated mDCs exhibited up-regulations of OX40L and ICOSL, but down-regulation of PDL1 in NP. Moreover, the IL-17RB, ST2 and TSLPR levels on mDCs were positively correlated with IL-25, IL-33 and TSLP mRNA levels, respectively, in NP. Furthermore, IL-17RB and ST2 expressions on mDCs were correlated with the IL-5 mRNA level as well as eosinophil number in NP. Importantly, the IL-17RB expression on mDCs and the OX40L expression on activated mDCs in NP were positively correlated with CT score and total nasal symptom score. Conclusions Increased expressions of IL-17RB and ST2 on mDCs are associated with enhanced local Th2 inflammation in NP, suggesting that mDCs might play a role in IL-25- and IL-33-induced type 2 responses and eosinophilic inflammation in NP. Electronic supplementary material The online version of this article (10.1186/s13601-018-0237-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Rui Zheng
- 1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.,Guangzhou key Laboratory of Otorhinolarygology, Guangzhou, 510080 China
| | - Dan Wang
- 1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.,Guangzhou key Laboratory of Otorhinolarygology, Guangzhou, 510080 China
| | - Kai Wang
- 3Department of Otorhinolaryngology-Head and Neck Surgery, First People's Hospital of Foshan, Foshan, 528000 China
| | - Wen-Xiang Gao
- 1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.,Guangzhou key Laboratory of Otorhinolarygology, Guangzhou, 510080 China
| | - Qin-Tai Yang
- 4Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630 China
| | - Li-Jie Jiang
- 1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.,Guangzhou key Laboratory of Otorhinolarygology, Guangzhou, 510080 China
| | - Min Zhou
- 1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.,Guangzhou key Laboratory of Otorhinolarygology, Guangzhou, 510080 China
| | - Yu-Jie Cao
- 1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.,Guangzhou key Laboratory of Otorhinolarygology, Guangzhou, 510080 China
| | - Jianbo Shi
- 1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.,Guangzhou key Laboratory of Otorhinolarygology, Guangzhou, 510080 China
| | - Yueqi Sun
- 1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080 Guangdong China.,Guangzhou key Laboratory of Otorhinolarygology, Guangzhou, 510080 China
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Lou H, Zhang N, Bachert C, Zhang L. Highlights of eosinophilic chronic rhinosinusitis with nasal polyps in definition, prognosis, and advancement. Int Forum Allergy Rhinol 2018; 8:1218-1225. [PMID: 30296011 PMCID: PMC6282610 DOI: 10.1002/alr.22214] [Citation(s) in RCA: 153] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Revised: 07/26/2018] [Accepted: 09/01/2018] [Indexed: 12/29/2022]
Abstract
Background Tissue eosinophils are characteristic of inflammation in most but not all patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and may be useful for defining subgroups and making treatment choices. However, no consistent diagnostic criteria for CRSwNP with eosinophilic inflammation have been established. Methods Related literature review was performed and current developments in the diagnosis of eosinophilic CRSwNP were summarized. Details in histopathology, definition of tissue eosinophilia, eosinophil as an indicator of disease recurrence, eosinophilic shift, and related biomarkers in CRSwNP are included in this review article. Results Mucosal eosinophilia exhibits significant geographic and ethnic differences and may increase over time. Tissue eosinophilia can be defined using a cutoff value based on reference values from healthy mucosa, but typical disease‐specific values should also be employed to increase sensitivity and specificity for clinical use. Recent developments highlight the diagnostic criteria for eosinophilic CRSwNP based on cluster analysis, which were also associated with clinical outcomes. Additionally, some promising eosinophil‐relevant biomarkers, such as eosinophilic cation protein and interleukin 5 (IL‐5), may be clinically applied as diagnostic or predictive tools for CRSwNP in the future. Conclusion Sinonasal tissue eosinophilia is present in a majority of CRSwNP patients but is currently more common in the West than in the East. Cutoff values of eosinophils as the diagnostic criteria of eosinophilic CRSwNP are subject to change with geographic and ethnic differences over time. It will be important to identify validated eosinophil‐related biomarkers in different continents/countries for future research and for the introduction of precision medicine.
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Affiliation(s)
- Hongfei Lou
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
| | - Nan Zhang
- Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
| | - Claus Bachert
- Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China.,Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China
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Chitsuthipakorn W, Seresirikachorn K, Sommer DD, McHugh T, Snidvongs K. Endotypes of Chronic Rhinosinusitis Across Ancestry and Geographic Regions. Curr Allergy Asthma Rep 2018; 18:46. [PMID: 29995271 DOI: 10.1007/s11882-018-0800-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Preliminary studies have suggested differences in endotypes of chronic rhinosinusitis (CRS) across ancestry/ethnic groups. Eosinophilic CRS (ECRS) is the predominant subtype for Western/European ancestry CRS patients and non-eosinophilic CRS (nECRS) for Asian patients. This review aims to re-analyze CRS endotypes across ancestry populations using one consistent criteria to existing data. RECENT FINDINGS Although tissue eosinophilia is the most commonly used criterion for ECRS, various cut-off points are suggested. Surrogate markers have been extensively studied. Sixty-six cohorts with study criteria were included with a total of 8557 patients. Raw data from 11 studies 544 patients were re-analyzed using number of tissue eosinophils. At lower cut-off values of ≥ 5 and ≥ 10 cells/HPF, most patients of Asian and Western/European ancestry were classified as ECRS without difference. In contrast, at cut-off points of ≥ 70 and ≥ 120 cells/HPF, the majority of both groups became reclassified as nECRS. After applying one consistent criteria to existing data, differences across ancestry and geographic populations in endotypes of CRS were no longer evident.
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Affiliation(s)
| | - Kachorn Seresirikachorn
- Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Prathumwan, Bangkok, 10330, Thailand.,Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Doron D Sommer
- Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, McMaster University, Hamilton, ON, Canada
| | - Tobial McHugh
- Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, McMaster University, Hamilton, ON, Canada
| | - Kornkiat Snidvongs
- Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Prathumwan, Bangkok, 10330, Thailand. .,Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
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Zhang Y, Gevaert E, Lou H, Wang X, Zhang L, Bachert C, Zhang N. Chronic rhinosinusitis in Asia. J Allergy Clin Immunol 2017; 140:1230-1239. [PMID: 28987810 DOI: 10.1016/j.jaci.2017.09.009] [Citation(s) in RCA: 143] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 09/27/2017] [Accepted: 09/27/2017] [Indexed: 01/05/2023]
Abstract
Chronic rhinosinusitis (CRS), although possibly overdiagnosed, is associated with a high burden of disease and is often difficult to treat in those truly affected. Recent research has demonstrated that inflammatory signatures of CRS vary around the world, with less eosinophilic and more neutrophilic inflammation found in Asia compared with Europe and North America. Although in the Western world about 80% of nasal polyps carry a type 2 signature, this might be between 20% and 60% in China and Korea or Thailand, respectively. These differences are associated with a lower asthma comorbidity and risk of disease recurrence after surgery in the Asian population. As a hallmark of severe type 2 inflammation, eosinophils attacking Staphylococcus aureus at the epithelial barrier have been described recently; they also can be found in a subgroup of Asian patients with nasal polyps. Furthermore, the percentage of type 2 signature disease in patients with CRS is dramatically increasing ("eosinophilic shift") in several Asian countries over the last 20 years. Establishing an accurate diagnosis along with considering the current and shifting patterns of inflammation seen in Asia will enable more effective selection of appropriate pharmacotherapy, surgical therapy, and eventually biotherapy. Determining the causes and pathophysiology for this eosinophilic shift will require additional research.
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Affiliation(s)
- Yuan Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Elien Gevaert
- Upper Airways Research Laboratory and Department of Oto-Rhino-Laryngology, Ghent University and Ghent University Hospital, Ghent, Belgium
| | - Hongfei Lou
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Xiangdong Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Beijing, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.
| | - Claus Bachert
- Upper Airways Research Laboratory and Department of Oto-Rhino-Laryngology, Ghent University and Ghent University Hospital, Ghent, Belgium; Division of ENT Diseases, CLINTEC, Karolinska Institute, University of Stockholm, Stockholm, Sweden.
| | - Nan Zhang
- Upper Airways Research Laboratory and Department of Oto-Rhino-Laryngology, Ghent University and Ghent University Hospital, Ghent, Belgium
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Gong GQ, Ren FF, Wang YJ, Wan L, Chen S, Yuan J, Yang CM, Liu BH, Kong WJ. Expression of IL-17 and syndecan-1 in nasal polyps and their correlation with nasal polyps. ACTA ACUST UNITED AC 2017; 37:412-418. [DOI: 10.1007/s11596-017-1749-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 04/25/2017] [Indexed: 01/13/2023]
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Shin SH, Kim YH, Ye MK, Choi SY. Immunopathologic Characteristics of Nasal Polyps in Adult Koreans: A Single-Center Study. Am J Rhinol Allergy 2017; 31:168-173. [DOI: 10.2500/ajra.2017.31.4423] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background Chronic rhinosinusitis with nasal polyps (NP) (CRSwNP) is classified into eosinophilic and noneosinophilic types based on the level of tissue eosinophilia. The immunopathologic features of Western and Asian CRSwNP differ. Objectives The aim of this study was to investigate the immunopathologic characteristics of Korean patients with eosinophilic NP versus noneosinophilic NP and those with atopic NP versus nonatopic NP. Methods Tissue samples were collected from 81 patients with NP and 24 controls. The clinical characteristics of all the patients were analyzed. Tissues were investigated for expression of chemical mediators, including interleukin (IL) 5, IL-10, IL-17, interferon-γ, and tumor growth factor-β1; transcription factors, including GATA binding protein 3 (GATA-3), forkhead box P3 (Foxp3), retinoic acid–related orphan receptor C (RORC), and T-box transcription factor (T-bet), and extracellular matrix, including collagen type I, fibronectin, tissue inhibitor of metalloproteinase 1, and matrix metalloproteinase (MMP) 9. Results Although the clinical characteristics differed between eosinophilic and noneosinophilic NPs, atopic status did not affect the clinical findings of CRSwNP. Both T-helper 1 and 2 cytokines increased significantly in patients with eosinophilic NP, but atopic status did not affect the expression of any of the chemical mediators. GATA-3 messenger RNA (mRNA) expression increased significantly in patients with eosinophilic NP, and RORC mRNA expression increased significantly in patients with noneosinophilic NP. T-bet, RORC, and Foxp3 mRNA expression increased significantly in patients with nonatopic NP. Fibronectin and MMP-9 mRNA expression increased significantly in patients with noneosinophilic NP, whereas only MMP-9 mRNA increased significantly in patients with eosinophilic and those with noneosinophilic NP. Conclusion The immunopathologic characteristics differed between eosinophilic NP and noneosinophilic NP and between atopic NP and nonatopic NP. The different underlying pathogenic processes may influence the development of Korean NP.
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Affiliation(s)
- Seung-Heon Shin
- Department of Otolaryngology—Head and Neck Surgery, School of Medicine, Catholic University of Daegu, Daegu, Korea
| | - Yee-Hyuk Kim
- Department of Otolaryngology—Head and Neck Surgery, School of Medicine, Catholic University of Daegu, Daegu, Korea
| | - Mi-Kyung Ye
- Department of Otolaryngology—Head and Neck Surgery, School of Medicine, Catholic University of Daegu, Daegu, Korea
| | - Sung-Yong Choi
- Department of Otolaryngology—Head and Neck Surgery, School of Medicine, Catholic University of Daegu, Daegu, Korea
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Tsybikov NN, Egorova EV, Kuznik BI, Fefelova EV, Magen E. Neuron-specific enolase in nasal secretions as a novel biomarker of olfactory dysfunction in chronic rhinosinusitis. Am J Rhinol Allergy 2016; 30:65-9. [PMID: 26867533 DOI: 10.2500/ajra.2016.30.4264] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Olfactory dysfunction is a diagnostic criterion for chronic rhinosinusitis (CRS). During chronic inflammation and olfactory neuronal damage in CRS, it is likely that neuron-specific enolase (NSE) can leak into nasal secretions (NS) and serum. Therefore, we postulated that NSE levels in NS and in circulation may be indicative of olfactory dysfunction in CRS. OBJECTIVE To evaluate the relationship between the NS and serum concentrations of NSE with olfactory dysfunction in subjects with CRS. METHODS The patients with CRS were classified into two groups, depending on the presence of polyps: CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). A group of age- and sex-matched healthy volunteers served as controls. Olfactory function assessment was performed by using Sniffin' Sticks. NSE concentrations in serum and NS were analyzed by using the enzyme immunometric assay kit specific for the γ subunit. RESULTS The study included 46 patients with CRSsNP, 25 women (54.3%) and 21 men (45.7%), mean (standard deviation [SD]) age, 34.1 ± 12.3 years; and 54 patients with CRSwNP, 24 women (44.4%) and 30 men (55.6%), mean (SD) age, 37.9 ± 17.5 years. A group of 40 healthy volunteers who were matched for age and sex served as controls. Significantly higher serum and NS levels of NSE were measured in patients with CRS compared with healthy controls (p < 0.001). In the CRSwNP group, both mean (SD) serum (83.5 ± 37.6 ng/mL) and mean (SD) NS (6.1 ± 2.3 ng/mL) levels of NSE were significantly higher than in the CRSsNP group (46.4 ± 7.3 ng/mL [p < 0.001] and 1.7 ± 0.5 ng/mL [p < 0.001], respectively). In both the CRSsNP and CRSwNP groups (but not in the healthy controls), significant negative correlations between NS NSE levels and TDI scores (r = -0.63, p < 0.001 for the CRSwNP group, and r = -0.51, p < 0.001 for CRSsNP group) were observed, which meant that higher NSE was associated with worse olfactory function. CONCLUSIONS The study demonstrated a contribution of CRS to NSE and olfactory dysfunction.
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Affiliation(s)
- Namjil N Tsybikov
- Pathophysiology Department, 2Normal Physiology Department, Chita Medical Academy, Chita, Russia
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Pathogenesis of eosinophilic chronic rhinosinusitis. JOURNAL OF INFLAMMATION-LONDON 2016; 13:11. [PMID: 27053925 PMCID: PMC4822241 DOI: 10.1186/s12950-016-0121-8] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Accepted: 04/01/2016] [Indexed: 01/12/2023]
Abstract
Eosinophilic chronic rhinosinusitis (ECRS) is considered a refractory and intractable disease. Patients with ECRS present with thick mucus production, long-term nasal congestion, loss of sense of smell, and intermittent acute exacerbations secondary to bacterial infections. Despite medical and surgical interventions, there is a high rate of recurrence with significant impairment to quality of life. The recent increasing prevalence of ECRS in south Asian countries and the strong tendency of ECRS to reoccur after surgery should be considered. The majority of cases need repeat surgery, and histological examinations of these cases show eosinophilic-dominant inflammation. The degradation and accumulation of eosinophils, release of cytokines, and mucus secretion have important roles in the pathogenesis of ECRS. ECRS differs from non-ECRS, in which eosinophils are not involved in the pathogenesis of the disease, and also in terms of many clinical characteristics, blood examination and nasal polyp histological findings, clinical features of the disease after surgery, efficacy of medications, and computed tomography findings. This review describes the clinical course, diagnosis, and treatment of ECRS as well as its pathophysiology and the role of eosinophils, mucus, cytokines, and other mediators in the pathogenesis of ECRS.
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Regulatory effect of TLR3 signaling on staphylococcal enterotoxin-induced IL-5, IL-13, IL-17A and IFN-γ production in chronic rhinosinusitis with nasal polyps. Allergol Int 2016; 65:96-102. [PMID: 26666485 DOI: 10.1016/j.alit.2015.08.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 08/21/2015] [Accepted: 08/31/2015] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Toll-like receptor 3 (TLR3) is expressed in upper airways, however, little is known regarding whether Toll-like receptor 3 (TLR3) signals exert a regulatory effect on the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), especially on eosinophilic inflammation. We sought to investigate the effect of Poly(IC), the ligand for TLR3, on cytokine production by dispersed nasal polyp cells (DNPCs). METHODS DNPCs were pretreated with or without Poly(IC), and were then cultured in the presence or absence of staphylococcal enterotoxin B (SEB), following which the levels of IL-5, IL-10, IL-13, IL-17A and interferon (IFN)-γ in the supernatant were measured. To determine the involvement of IL-10 and cyclooxygenase in Poly(IC)-mediated signaling, DNPCs were treated with anti-IL-10 monoclonal antibody and diclofenac, the cyclooxygenase inhibitor, respectively. Poly(IC)-induced prostaglandin E2 (PGE2) production was also determined. RESULTS Exposure to Poly(IC) induced a significant production of IL-10, but not of IL-5, IL-13, IL-17A or IFN-γ by DNPCs. Pretreatment with Poly(IC) dose-dependently inhibited SEB-induced IL-5, IL-13 and IL-17A, but not IFN-γ production. Neutralization of IL-10 significantly abrogated the inhibitory effect of Poly(IC). Treatment with diclofenac also abrogated the inhibitory effect of Poly(IC) on SEB-induced IL-5 and IL-13 production. However, unlike exposure of diclofenac-treated DNPCs to lipopolysaccharide, the ligand for TLR4, exposure of these cells to Poly(IC) did not enhance IL-5 or IL-13 production. Poly(IC) did not significantly increase PGE2 production by DNPCs. CONCLUSIONS These results suggest that TLR3 signaling regulates eosinophilia-associated cytokine production in CRSwNP, at least in part, via IL-10 production.
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Ramakrishnan VR. Editorial: Insights into disease pathogenesis and novel therapeutics. Am J Rhinol Allergy 2015; 28:93-4. [PMID: 24717940 DOI: 10.2500/ajra.2014.28.2016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Okano M, Kariya S, Ohta N, Imoto Y, Fujieda S, Nishizaki K. Association and management of eosinophilic inflammation in upper and lower airways. Allergol Int 2015; 64:131-8. [PMID: 25838087 DOI: 10.1016/j.alit.2015.01.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Revised: 01/06/2015] [Accepted: 01/08/2015] [Indexed: 01/18/2023] Open
Abstract
This review discussed the contribution of eosinophilic upper airway inflammation includes allergic rhinitis (AR) and chronic rhinosinusitis (CRS) to the pathophysiology and course of asthma, the representative counterpart in the lower airway. The presence of concomitant AR can affect the severity of asthma in patients who have both diseases; however, it is still debatable whether the presence of asthma affects the severity of AR. Hypersensitivity, obstruction and/or inflammation in the lower airway can be detected in patients with AR without awareness or diagnosis of asthma, and AR is known as a risk factor for the new onset of wheeze and asthma both in children and adults. Allergen immunotherapy, pharmacotherapy and surgery for AR can contribute to asthma control; however, a clear preventive effect on the new onset of asthma has been demonstrated only for immunotherapy. Pathological similarities such as epithelial shedding are also seen between asthma and CRS, especially eosinophilic CRS. Abnormal sinus findings on computed tomography are seen in the majority of asthmatic patients, and asthmatic patients with CRS show a significant impairment in Quality of Life (QOL) and pulmonary function as compared to those without CRS. Conversely, lower airway inflammation and dysfunction are seen in non-asthmatic patients with CRS. Treatments for CRS that include pharmacotherapy such as anti-leukotrienes, surgery, and aspirin desensitization show a beneficial effect on concomitant asthma. Acting as a gatekeeper of the united airways, the control of inflammation in the nose is crucial for improvement of the QOL of patients with co-existing AR/CRS and asthma.
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Affiliation(s)
- Mitsuhiro Okano
- Department of Otolaryngology - Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
| | - Shin Kariya
- Department of Otolaryngology - Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Nobuo Ohta
- Department of Otolaryngology, Yamagata University School of Medicine, Yamagata, Japan
| | - Yoshimasa Imoto
- Department of Otorhinolaryngology - Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Shigeharu Fujieda
- Department of Otorhinolaryngology - Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Kazunori Nishizaki
- Department of Otolaryngology - Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
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Wang ET, Zheng Y, Liu PF, Guo LJ. Eosinophilic chronic rhinosinusitis in East Asians. World J Clin Cases 2014; 2:873-882. [PMID: 25516863 PMCID: PMC4266836 DOI: 10.12998/wjcc.v2.i12.873] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Revised: 08/28/2014] [Accepted: 09/17/2014] [Indexed: 02/05/2023] Open
Abstract
Chronic rhinosinusitis (CRS) is a common disease worldwide, with a prevalence rate of 5%-15% in the general population. CRS is currently classified into two types: CRS with and without nasal polyps. CRS may also be divided into eosinophilic CRS (ECRS) and non-ECRS subtypes based on the presence of tissue eosinophilic infiltration or not. There are significant geographic and ethnic differences in the tissue eosinophilic infiltration, which is predominant in Western white patients and less common in East Asians, despite an increasing tendency for its prevalence in East Asia countries. ECRS differs significantly from non-ECRS in clinical characteristics, treatment outcomes and strategies, and underlying pathogenic mechanisms. ECRS commonly demonstrates more severe symptoms, polyp diseases with a higher incidence of bilateral polyps and sinonasal diseases on computed tomography, and the increase in blood eosinophils. ECRS is considered a special and recalcitrant subtype of CRS, commonly with poor treatment outcomes compared to non-ECRS. The differentiation of specific subtypes and clinical features of CRS will be important for developing novel treatment strategies and improving treatment outcomes for individual phenotypes of CRS. This review discusses clinical features, diagnosis, treatment and prognosis of ECRS in East Asians.
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